New Research Highlights Potential of Novel Alpha-Pharmaceutical in Targeting and Killing Breast Cancer Cells
News Jun 19, 2009
Algeta ASA, the cancer therapeutics company, announces results of new research demonstrating that the alpha particle emitter thorium-227 (227Th) linked to the monoclonal antibody trastuzumab (Herceptin) selectively targets and kills breast cancer cells.
The research, which was conducted by a team of scientists from the Norwegian Radium Hospital led by Dr. Jostein Dahle in collaboration with Algeta, was presented at the 56th annual Society for Nuclear Medicine 2009 meeting.
This is the first time that the targeted cancer cell-killing effect of 227Th-trastuzumab has been presented and suggests that further studies be conducted with this alpha-pharmaceutical as a novel treatment for breast cancer.
Trastuzumab, known commercially as Herceptin and marketed by Roche/Genentech, targets tumor cells presenting the HER-2 receptor on their cell surface, and tumors in approximately 25% of breast cancer patients carry this marker.
The presentations given at SNM meeting pointed to three key findings of the effects of 227Th-trastuzumab on breast cancer cells expressing HER-2:
• Target specificity: 227Th-trastuzumab selectively targeted and bound HER-2 presenting tumor cells in vitro and in mice with HER-2 positive tumors
• Tumor cell-killing effect: 227Th-trastuzumab exerted a measurable and dose-dependent therapeutic effect by killing HER-2 positive breast cancer cells to which it was bound and had a significant effect on tumor growth at low doses, and
• Indication of safety: Blood toxicity of 227Th-trastuzumab, determined from measuring white blood cell counts in the mouse models, was modest and temporary. This is believed to be a result of the targeted and localized mode of action of 227Th-trastuzumab.
Thorium-227, is an element (radionuclide) that emits high-energy alpha particles. Such elements are of considerable interest in the treatment of cancer as they are potent at killing tumor cells but have a highly localized effect. By linking thorium-227 to tumor-targeting molecules such as monoclonal antibodies, Algeta has the potential to create a pipeline of new generation alpha-pharmaceuticals with the potential to specifically seek and destroy cancers while minimizing damage to surrounding healthy tissues.
This technology was highlighted at the conference by Michael J. Welch, professor of radiology at the Washington University School of Medicine's Mallinckrodt Institute of Radiology in St. Louis (MI), and a leading US radiological scientist, in the "Basic Science Summary Session - Radiopharmaceutical Sciences.
In this session, Prof. Welch noted that linking thorium-227 to monoclonal antibodies had generated “impressive results from this new alpha radionuclide.”